How to manage a patient with acute cystitis and hematuria while on Eliquis (apixaban)?

Management of Acute Cystitis with Hematuria in Patients on Eliquis (Apixaban)

Do not discontinue apixaban for uncomplicated acute cystitis with hematuria; instead, treat the infection with first-line antibiotics while monitoring for signs of severe bleeding, as the hematuria is typically due to the infection itself rather than anticoagulant-related bleeding. 1, 2

Initial Assessment and Diagnosis

• Obtain urinalysis and urine culture before initiating antibiotics to confirm the diagnosis and guide therapy, particularly important in patients on anticoagulation where hematuria requires documentation 1, 3
• Look specifically for dysuria, frequency, urgency, and suprapubic tenderness as classic cystitis symptoms 1, 3
• Hematuria in the setting of acute cystitis symptoms is typically infectious in origin, not primarily anticoagulant-related, especially when accompanied by dysuria and other UTI symptoms 1
• Rule out more serious complications: assess for fever (suggesting pyelonephritis), severe abdominal pain, or signs of bladder outlet obstruction 4, 5

Anticoagulation Management

Continue apixaban without interruption for uncomplicated cystitis with hematuria 2. The FDA label for apixaban indicates discontinuation only for "active pathological hemorrhage," which uncomplicated hemorrhagic cystitis does not constitute 2.

• Monitor for signs of severe bleeding: hemodynamic instability, significant drop in hemoglobin, clot retention causing urinary obstruction, or oliguria 2, 6, 7
• If severe hemorrhagic cystitis develops with hemodynamic compromise, consider temporary discontinuation and consult urology urgently 2, 7
• The anticoagulant effect persists for at least 24 hours after the last dose (approximately two half-lives), which is relevant if discontinuation becomes necessary 2

Important caveat: While rare case reports describe anticoagulant-related nephropathy with apixaban presenting as acute kidney injury with glomerular hematuria and red blood cell casts 8, this is distinct from infectious hemorrhagic cystitis and would present with renal dysfunction rather than isolated lower urinary tract symptoms.

Antibiotic Treatment

Initiate first-line antibiotic therapy immediately after obtaining cultures 1, 3:

• Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days (preferred due to minimal resistance and collateral damage) 1

• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days if local E. coli resistance is <20% 1

• Fosfomycin trometamol 3 g single dose as alternative, though may have slightly inferior efficacy 1

• Treat for no longer than 7 days total to minimize antibiotic exposure and resistance development 1

• Avoid fluoroquinolones as first-line therapy; reserve for resistant organisms or when other agents cannot be used 1, 3

Monitoring and Follow-Up

• Ensure adequate hydration (>8 glasses of water daily) to promote urine flow and reduce clot formation risk 1, 7
• Monitor for symptom resolution within 48-72 hours of antibiotic initiation 1
• If symptoms persist or worsen despite appropriate antibiotics, obtain repeat urine culture and consider imaging to exclude complications like emphysematous cystitis or urinary obstruction 1, 4
• Watch for signs of upper tract involvement (fever, flank pain, nausea) that would require escalation to pyelonephritis treatment 1

When to Escalate Care

Urgent urology consultation is indicated for 2, 7:

• Clot retention with urinary obstruction requiring continuous bladder irrigation
• Hemodynamic instability or significant blood loss requiring transfusion
• Persistent gross hematuria despite appropriate antibiotic therapy and infection resolution
• Development of acute kidney injury in the setting of hematuria (consider anticoagulant-related nephropathy) 8

Common Pitfalls to Avoid

• Do not routinely discontinue anticoagulation for simple hemorrhagic cystitis, as this increases thromboembolic risk without addressing the underlying infection 2
• Do not treat asymptomatic bacteriuria if discovered incidentally; only symptomatic infections require treatment 1, 3
• Do not assume hematuria is solely due to anticoagulation without evaluating for infectious or other causes, especially when accompanied by dysuria 1, 4
• Avoid empiric broad-spectrum antibiotics when first-line agents are appropriate based on local resistance patterns 1, 3